Effect of Divergence Time and Recombination Rate on Molecular Evolution of Drosophila INE-1 Transposable Elements and Other Candidates for Neutrally Evolving Sites

  • Jun Wang
  • Peter D. Keightley
  • Daniel L. HalliganEmail author


Interspecies divergence of orthologous transposable element remnants is often assumed to be simply due to genetic drift of neutral mutations that occurred after the divergence of the species. However, divergence may also be affected by other factors, such as variation in the mutation rate, ancestral polymorphisms, or selection. Here we attempt to determine the impact of these forces on divergence of three classes of sites that are often assumed to be selectively unconstrained (INE-1 TE remnants, sites within short introns, and fourfold degenerate sites) in two different pairwise comparisons of Drosophila (D. melanogaster vs. D. simulans and D. simulans vs. D. sechellia). We find that divergence of these three classes of sites is strongly influenced by the recombination environment in which they are located, and this is especially true for the closer D. simulans vs. D. sechellia comparison. We suggest that this is mainly a result of the contribution of ancestral polymorphisms in different recombination regions. We also find that intergenic INE-1 elements are significantly more diverged than intronic INE-1 in both pairwise comparisons, implying the presence of either negative selection or lower mutation rates in introns. Furthermore, we show that substitution rates in INE-1 elements are not associated with the length of the noncoding sequence in which they are located, suggesting that reduced divergence in long noncoding sequences is not due to reduced mutation rates in these regions. Finally, we show that GC content for each site within INE-1 sequences has evolved toward an equilibrium value (∼33%) since insertion.


INE-1 Drosophila Neutral evolution Substitution rate Crossing-over 



We are grateful to the Genome Sequence Center, WUSTL School of Medicine, the Broad Institute of MIT and Harvard, and the Berkeley Drosophila Genome Project for providing the genome sequences we analyzed in this study. We also thank Flybase and NCBI for providing genome annotation data. We thank Toby Johnson, Daniel Gaffney, and Brian Charlesworth for helpful comments. J.W. was supported by the Dorothy Hodgkin Postgraduate Studentship Award. Funding for D.L.H. was provided by the Wellcome Trust.

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  1. Akashi H (1995) Inferring weak selection from patterns of polymorphism and divergence at “silent” sites in Drosophila DNA. Genetics 139:1067–1076PubMedGoogle Scholar
  2. Aquado CF, Begun DJ, Kindahl EC (1994) Selection, recombination, and DNA polymorphism in Drosophila. In: Golding B (ed) Non-neutral evolution: theories and molecular data. Chapman and Hall, London, pp 46–56Google Scholar
  3. Begun DJ, Aquadro CF (1992) Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature 356:519–520PubMedCrossRefGoogle Scholar
  4. Berg DE, Howe MM (1989) Mobile DNA. ASM Press, Herndon, VAGoogle Scholar
  5. Betancourt AJ, Presgraves DC (2002) Linkage limits the power of natural selection in Drosophila. Proc Natl Acad Sci USA 99:13616–13620PubMedCrossRefGoogle Scholar
  6. Bray N, Pachter L (2004) MAVID: constrained ancestral alignment of multiple sequences. Genome Res 14:693–699PubMedCrossRefGoogle Scholar
  7. Charlesworth B (1996) Background selection and patterns of genetic diversity in Drosophila melanogaster. Genet Res 68:131–149PubMedGoogle Scholar
  8. Charlesworth B, Langley CH (1989) The population genetics of Drosophila transposable elements. Annu Rev Genet 23:251–287PubMedCrossRefGoogle Scholar
  9. Charlesworth B, Lapid A (1989) A study of ten transposable elements on X chromosomes from a population of Drosophila melanogaster. Genet Res 54:113–125PubMedGoogle Scholar
  10. Charlesworth B, Lapid A, Canada D (1992) The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. I. Element frequencies and distribution. Genet Res 60:103–114PubMedGoogle Scholar
  11. Deaconescu AM, Chambers AL, Smith AJ, et al. (2006) Structural basis for bacterial transcription-coupled DNA repair. Cell 124:507–520PubMedCrossRefGoogle Scholar
  12. Deininger PL, Batzer MA (2002) Mammalian retroelements. Genome Res 12:1455–1465PubMedCrossRefGoogle Scholar
  13. Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658PubMedCrossRefGoogle Scholar
  14. Felsenstein J (1974) The evolutionary advantage of recombination. Genetics 78:737–756PubMedGoogle Scholar
  15. Gaffney DJ, Keightley PD (2006) Genomic selective constraints in murid noncoding DNA. PLoS Genet 2:e204PubMedCrossRefGoogle Scholar
  16. Haddrill PR, Charlesworth B, Halligan DL, Andolfatto P (2005) Patterns of intron sequence evolution in Drosophila are dependent upon length and GC content. Genome Biol 6:R67PubMedCrossRefGoogle Scholar
  17. Haddrill PR, Halligan DL, Tomaras D, Charlseworth B (2007) Reduced efficacy of selection in regions of the Drosophila genome that lack crossing over. Genome Biol 8:R18PubMedCrossRefGoogle Scholar
  18. Halligan DL, Keightley PD (2006) Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison. Genome Res 16:875–884PubMedCrossRefGoogle Scholar
  19. Hardison RC, Roskin KM, Yang S, et al. (2003) Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution. Genome Res 13:13–26PubMedCrossRefGoogle Scholar
  20. Hellmann I, Ebersberger I, Ptak SE, Pääbo S, Przeworski M (2003) A neutral explanation for the correlation of diversity with recombination rates in humans. Am J Hum Genet 72:1527–1535PubMedCrossRefGoogle Scholar
  21. Hey J, Kliman RM (2002) Interactions between natural selection, recombination and gene density in the genes of Drosophila. Genetics 160:595–608PubMedGoogle Scholar
  22. Hill WG, Robertson A (1966) The effect of linkage on limits to artificial selection. Genet Res 8:269–294PubMedGoogle Scholar
  23. Jakubczak JL, Xiong Y, Eickbush TH (1990) Type I (R1) and type II (R2) ribosomal DNA insertions of Drosophila melanogaster are retrotransposable elements closely related to those of Bombyx mori. J Mol Biol 212:37–52PubMedCrossRefGoogle Scholar
  24. Jensen MA, Charlesworth B, Kreitman M (2002) Patterns of genetic variation at a chromosome 4 locus of Drosophila melanogaster and D. simulans. Genetics 160:493–507PubMedGoogle Scholar
  25. Jordan IK, Rogozin IB, Glazko GV, Koonin EV (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19:68–72PubMedCrossRefGoogle Scholar
  26. Kapitonov VV, Jurka J (1999) DNAREP1_DM. Repbase update release 3.4. Available at:
  27. Kapitonov VV, Jurka J (2003) Molecular paleontology of transposable elements in the Drosophila melanogaster genome. Proc Natl Acad Sci USA 100:6569–6574PubMedCrossRefGoogle Scholar
  28. Kaplan NL, Hudson RR, Langley CH (1989) The “hitch-hiking effect” revisited. Genetics 123(4):887–899PubMedGoogle Scholar
  29. Kazazian HH (2004) Mobile elements: drivers of genome evolution. Science 303(5664):1626–1632PubMedCrossRefGoogle Scholar
  30. Kimura M (1980) A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120PubMedCrossRefGoogle Scholar
  31. Kirby DA, Muse SV, Stephan W (1995) Maintenance of pre-mRNA secondary structure by epistatic selection. Proc Natl Acad Sci USA 92:9047–9051PubMedCrossRefGoogle Scholar
  32. Kliman RM, Hey J (1993) Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol 10:1239–1258PubMedGoogle Scholar
  33. LePage DF, Church DM, Millie E, Hassold TJ, Conlon RA (2000) Rapid generation of nested chromosomal deletions on mouse chromosome 2. Proc Natl Acad Sci USA 97:10471–10476PubMedCrossRefGoogle Scholar
  34. Lercher MJ, Hurst LD (2002) Human SNP variability and mutation rate are higher in regions of high recombination. Trends Genet 18:337–340PubMedCrossRefGoogle Scholar
  35. Marais G, Domazet-Loso T, Tautz D, Charlesworth B (2004) Correlated evolution of synonymous and nonsynonymous sites in Drosophila. J Mol Evol 59:771–779PubMedCrossRefGoogle Scholar
  36. Maynard-Smith J, Haigh J (1974) The hitch-hiking effect of a favorable gene. Genet Res 23:23–35CrossRefGoogle Scholar
  37. McDonald JF (1993) Evolution and consequences of transposable elements. Curr Opin Genet Dev 3:855–864PubMedCrossRefGoogle Scholar
  38. McVean GA, Vieira J (2001) Inferring parameters of mutation, selection and demography from patterns of synonymous site evolution in Drosophila. Genetics 157:245–257PubMedGoogle Scholar
  39. Moriyama EN, Powell JR (1996) Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol 13:261–277PubMedGoogle Scholar
  40. Moriyama EN, Powell JR (1997) Synonymous substitution rates in Drosophila: mitochondrial versus nuclear genes. J Mol Evol 45:378–391PubMedCrossRefGoogle Scholar
  41. Mozer BA, Benzer S (1994) Ingrowth by photoreceptor axons induces transcription of a retrotransposon in the developing Drosophila brain. Development 120:1049–1058PubMedGoogle Scholar
  42. Pardue ML, DeBaryshe PG (2003) Retrotransposons provide an evolutionarily robust non-telomerase mechanism to maintain telomeres. Annu Rev Genet 37:485–511PubMedCrossRefGoogle Scholar
  43. Petrov DA, Hartl DL (1999) Patterns of nucleotide substitution in Drosophila and mammalian genomes. Proc Natl Acad Sci USA 96:1475–1479PubMedCrossRefGoogle Scholar
  44. Presgraves DC (2005) Recombination enhances protein adaptation in Drosophila melanogaster. Curr Biol 15:1651–1656PubMedCrossRefGoogle Scholar
  45. Pyatkov KI, Shostak NG, Zelentsova ES, et al. (2002) Penelope retroelements from Drosophila virilis are active after transformation of Drosophila melanogaster. Proc Natl Acad Sci USA 99:16150–16155PubMedCrossRefGoogle Scholar
  46. Quesneville H, Bergman CM, Andrieu O, et al. (2005) Combined evidence annotation of transposable elements in genome sequences. PLoS Comput Biol 1:166–175PubMedCrossRefGoogle Scholar
  47. Shapiro JA, Huang W, Zhang C, Hubisz MJ, Lu J, Turissini DA, Fang S, Wang HY, Hudson RR, Nielsen R, Chen Z, Wu CI (2007) Adaptive genic evolution in the Drosophila genomes, Proc Natl Acad Sci USA 104(7):2271–2276PubMedCrossRefGoogle Scholar
  48. Singh ND, Petrov DA (2004) Rapid sequence turnover at an intergenic locus in Drosophila. Mol Biol Evol 21:670–680PubMedCrossRefGoogle Scholar
  49. Singh ND, Arndt PF, Petrov DA (2005a) Genomic heterogeneity of background substitutional patterns in Drosophila melanogaster. Genetics 169:709–722Google Scholar
  50. Singh ND, Davis JC, Petrov DA (2005b) Codon bias and noncoding GC content correlate negatively with recombination rate on the Drosophila X chromosome. J Mol Evol 61:315–324Google Scholar
  51. Slawson EE, Shaffer CD, Malone CD, et al. (2006) Comparison of dot chromosome sequences from D. melanogaster and D. virilis reveals an enrichment of DNA transposon sequences in heterochromatic domains. Genome Biol 7:R15PubMedCrossRefGoogle Scholar
  52. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680PubMedCrossRefGoogle Scholar
  53. van de Lagemaat LN, Landry JR, Mager DL, Medstrand P (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19:530–536PubMedCrossRefGoogle Scholar
  54. Venter JC, Adams MD, Myers EW, et al. (2001) The sequence of the human genome. Science 291:1304–1351PubMedCrossRefGoogle Scholar
  55. Wang J, Keightley PD, Johnson T (2006) MCALIGN2: faster, accurate global pairwise alignment of non-coding DNA sequences based on explicit models of indel evolution. BMC Bioinform 7:292CrossRefGoogle Scholar
  56. Waterston RH, Lindblad-Toh K, Birney E, et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562PubMedCrossRefGoogle Scholar
  57. White SE, Habera LF, Wessler SR (1994) Retrotransposons in the flanking regions of normal plant genes: a role for copia-like elements in the evolution of gene structure and expression. Proc Natl Acad Sci USA 91:11792–11796PubMedCrossRefGoogle Scholar
  58. Yang H-P, Hung T-L, You T-L, Yang T-H (2006) Genomewide comparative analysis of the highly abundant transposable element DINE-1 suggests a recent transpositional burst in Drosophila yakuba. Genetics 173(1):189–196PubMedCrossRefGoogle Scholar
  59. Yi S, Summers TJ, Pearson NM, Li W-H (2004) Recombination has little effect on the rate of sequence divergence in pseudoautosomal boundary 1 among humans and great apes. Genome Res 14:37–43PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jun Wang
    • 1
  • Peter D. Keightley
    • 1
  • Daniel L. Halligan
    • 1
    Email author
  1. 1.Institute of Evolutionary Biology, School of Biological SciencesUniversity of EdinburghEdinburghUK

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